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EGCG protects against homocysteine-induced human umbilical vein endothelial cells apoptosis by modulating mitochondrial-dependent apoptotic signaling and PI3K/Akt/eNOS signaling pathways

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Abstract

Homocysteine (Hcy) induced vascular endothelial injury leads to the progression of endothelial dysfunction in atherosclerosis. Epigallocatechin gallate (EGCG), a natural dietary antioxidant, has been applied to protect against atherosclerosis. However, the underlying protective mechanism of EGCG has not been clarified. The present study investigated the mechanism of EGCG protected against Hcy-induced human umbilical vein endothelial cells (HUVECs) apoptosis. Methyl thiazolyl tetrazolium assay (MTT), transmission electron microscope, fluorescent staining, flow cytometry, western blot were used in this study. The study has demonstrated that EGCG suppressed Hcy-induced endothelial cell morphological changes and reactive oxygen species (ROS) generation. Moreover, EGCG dose-dependently prevented Hcy-induced HUVECs cytotoxicity and apoptotic biochemical changes such as reducing mitochondrial membrane potential (MMP), decreasing Bcl-2/Bax protein ratio and activating caspase-9 and 3. In addition, EGCG enhanced the protein ratio of p-Akt/Akt, endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) formation in injured cells. In conclusion, the present study shows that EGCG prevents Hcy-induced HUVECs apoptosis via modulating mitochondrial apoptotic and PI3K/Akt/eNOS signaling pathways. Furthermore, the results indicate that EGCG is likely to represent a potential therapeutic strategy for atherosclerosis associated with Hyperhomocysteinemia (HHcy).

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Abbreviations

Hcy:

Homocysteine

EGCG:

Epigallocatechin gallate

HHcy:

Hyperhomocysteinemia

HUVEC:

Human umbilical vein endothelial cell

LDH:

Lactate dehydrogenase

MDA:

Malondialdehyde

SOD:

Superoxide dismutase

ROS:

Reactive oxygen species

MMP:

Mitochondrial membrane potential

Akt:

Protein kinase B

p-Akt:

Phosphorylated protein kinase B

eNOS:

Endothelial nitric oxide synthase

NO:

Nitric oxide

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Acknowledgements

This study was financially supported by the Natural Science Foundation of China (No. 30772601) and the University Innovation Team Project Foundation of Education Department of Liaoning Province (No. LT2013019).

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    Authors and Affiliations

    1. Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China

      Shumin Liu, Peng Chu, Hailong Li, Anil Ahsan, Ziru Zhou, Zonghui Zhang, Bin Sun, Jingjun Wu, Guozhu Han, Yuan Lin, Jinyong Peng & Zeyao Tang

    2. Pharmacy Department, Dalian Municipal Central Hospital, Dalian, China

      Zhengwu Sun & Yalin Xi

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    1. Shumin Liu
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    Correspondence to Zeyao Tang.

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    Shumin Liu, Zhengwu Sun and Peng Chu equally contributed to the work.

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    Liu, S., Sun, Z., Chu, P. et al. EGCG protects against homocysteine-induced human umbilical vein endothelial cells apoptosis by modulating mitochondrial-dependent apoptotic signaling and PI3K/Akt/eNOS signaling pathways. Apoptosis 22, 672–680 (2017). https://doi.org/10.1007/s10495-017-1360-8

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    • DOI: https://doi.org/10.1007/s10495-017-1360-8

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